The conversion of phenols to thiophenols, for example, the phenol group contained in salicylates, has been successfully carried out by the following scheme, for example, ##STR1##
Various aromatic or heteroaromatic thiophenols have been synthesized by this method. Yields of the expected product are generally good, and few limitations have been placed on the substitution of the starting phenol. See Newman, M. S. et al., J. Org. Chem., 31, 3980 (1966); Imada, I. et al., European Patent Application No. 26,000 (1981); Allen, R. C. et al., U.S. Pat. No. 3,878,225 (1975); and Carral, C. et al., Synthesis, 172(1984).
However, during the preparation of certain substituted thiosalicylic acids, we discovered, unexpectedly, that various substituted methyl salicylate N,N-dialkylthiocarbamates undergo a novel rearrangement to give the N,N-dialkyl 2-(methylthio)benzamides rather than the expected thiosalicylates. It happens that benzamides are useful intermediates for the preparation of known antiinflammatory and analgesic agents such as 5-aroyl-1,2-dihydro-3H-pyrrole-1-[1,2-a]pyrrolo-carboxylic acids and 3-aroyl-indol-1-ylacetic acids. See J. M. Muchoski et al., J. Med. Chem. 28(8), 1037(1985); and U.K. Pat. No. 1,260,868 respectively.
It was found that the same rearrangement takes place when various substituted 6-azasalicylate N,N-dialkylthiocarbamates were heated.
It is, therefore, the object of this invention to provide a novel process for the preparation of N,N-dialkyl-2-(methylthio)benzamides as useful precursor of pyrrole[1,2-a]pyrrolo-1-carboxylic acid derivatives and 3-aroyl-indol-1-ylacetic acids.